Human retroviruses, especially the human immunodeficiency viruses types 1 (HIV-1) and type 2 (HIV-2) have become important blood-borne pathogens. Although HIV-1 has clearly become important in much of the world, the distribution of HIV-2, which was discovered more recently, has not been fully ascertained outside of West Africa. Since HIV-2 is apparently less virulent than HIV-1, and also distributed to some extent outside Africa, including Massachusetts, the availability of screening test antigens that will detect HIV-2 with high efficiency and/or allow distinguishing HIV-1 and HIV-2 from each other will be increasingly important. We plan to use HIV-1 and/or HIV-2 specific probes in polymerase chain reaction (PCR) and the HIV-2 specific vpx protein and the vpu specific protein of HIV-1 in antigen/antibody studies to help distinguish these viruses. Other antigens of HIV-2 will also be evaluated for HIV-2, antibody screening including all the regulatory gene proteins, different domains of gp120, and proteins of the gag and pol genes. All of these antigens will be compared to each other and to the analogous HIV-1 antigens in the same manner that the different HIV-1 proteins and peptides have already been evaluated in our lab. Major emphasis will also be given to the issue of detecting HIV-1, HIV-2, HTLV-1 and/or HTLV-2 cells by PCR when multiple infections with two viruses occur in the same individual. Using both type specific antigens and PCR we will determine how sensitivity for detectability of either virus may be reduced in individuals that are dually infected. We already know that significantly rates of dual infection occur with an HIV and an HTLV in groups such as prostitutes and intravenous drug abusers and 3-5% of the HIV infected individuals in West Africa are infected with both HIV-1 and HIV-2. Emphasis will also be directed to an evaluation of the HIV-1 nef and vpu proteins (p27 and p16) to determine their potential usefulness in detecting early infections, before antibodies to most structural proteins are present. Recognizing that this "window of seroconversion" may be prolonged in people who are infected by sexual contact, such serological tests (and certainly PCR) may become increasingly important for screening. Individual sera from Africans with atypical Western blot or radioimmunoprecipitation results will be further evaluated for characterization according to HIV-1, HIV-2, or other (as yet undescribed) types as was done previously in our lab to identify HIV-2. For these and other studies will take advantage of our unique access to samples from West Africa, Central Africa, and African-Americans living in the Massachusetts/Rhode Island areas.